TY - JOUR
T1 - IFN-γ up-regulates the human C5a receptor (CD88) in myeloblastic U937 cells and related cell lines
AU - Burg, M.
AU - Martin, U.
AU - Rheinheimer, C.
AU - Kohl, J.
AU - Bautsch, W.
AU - Bottger, E. C.
AU - Klos, A.
PY - 1995/11/1
Y1 - 1995/11/1
N2 - On human mature monocytes the immunomodulator IFN-γ has been shown to down-regulate the receptor for the anaphylatoxic peptide C5a (CD88, C5aR). In this study, we show that in immature myelo-/monoblastic U937, HL60, and MonoMac6 cells, IFN-γ induces C5aR-ligand binding activity. In U937 cells, this induction cannot be blocked by the protein kinase C inhibitor staurosporine. An increase in free cytosolic Ca2+ upon ligand binding indicates functional coupling of this receptor in U937 and HL-60 cells. G- Proteins involved in this C5a responsiveness after IFN-γ induction are completely pertussis toxin sensitive. Our data suggest that an additional pertussis toxin-resistant pathway exists in U937 cells after induction by dibutyryl cAMP. However, this is not due to changes in the mRNA level of the pertussis toxin-insensitive G-protein subunit Gα16. Induction by dibutyryl cAMP, but not that by IFN-γ, resulted in C5a-dependent release of N-acetyl- β-D-glucosaminidase, further highlighting functional differences in the effects of the inducers. Our data show an IFN-γ-dependent increase in C5aR expression and suggest a maturation-related change in signaling of the C5aR, presumably at the level of receptor coupling.
AB - On human mature monocytes the immunomodulator IFN-γ has been shown to down-regulate the receptor for the anaphylatoxic peptide C5a (CD88, C5aR). In this study, we show that in immature myelo-/monoblastic U937, HL60, and MonoMac6 cells, IFN-γ induces C5aR-ligand binding activity. In U937 cells, this induction cannot be blocked by the protein kinase C inhibitor staurosporine. An increase in free cytosolic Ca2+ upon ligand binding indicates functional coupling of this receptor in U937 and HL-60 cells. G- Proteins involved in this C5a responsiveness after IFN-γ induction are completely pertussis toxin sensitive. Our data suggest that an additional pertussis toxin-resistant pathway exists in U937 cells after induction by dibutyryl cAMP. However, this is not due to changes in the mRNA level of the pertussis toxin-insensitive G-protein subunit Gα16. Induction by dibutyryl cAMP, but not that by IFN-γ, resulted in C5a-dependent release of N-acetyl- β-D-glucosaminidase, further highlighting functional differences in the effects of the inducers. Our data show an IFN-γ-dependent increase in C5aR expression and suggest a maturation-related change in signaling of the C5aR, presumably at the level of receptor coupling.
UR - http://www.scopus.com/inward/record.url?scp=0028973009&partnerID=8YFLogxK
M3 - Journal articles
C2 - 7594603
AN - SCOPUS:0028973009
SN - 0022-1767
VL - 155
SP - 4419
EP - 4426
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -
